This proposal is a collaborative, multi-disciplinary program involving researchers in the Departments of Medicine, Pathology, and Bioengineering at the University of Washington. Our objective is to investigate the feasibility of detecting Barrett's epithelium underneath squamous epithelium using optical coherence tomography (OCT). Barrett's esophagus is a premalignant condition found in 5% to 10% of patients with gastroesophageal reflux disease. Barrett's patients have a 30- to 50-fold increased risk of developing esophageal adenocarcinoma. Recently, a number of endoscopic treatments have been developed to ablate Barrett's epithelium. However, approximately 5% to 10% of patients have areas of residual Barrett's epithelium underneath the newly replaced squamous epithelium. This is a problematic condition since the underlying Barrett's is no longer visible to the endoscopist and the patient is still at risk for esophageal cancer. OCT is an emerging non-invasive diagnostic technique capable of cross-sectional imaging of tissue microstructure in real time. OCT imaging depth is 1-3 mm in most highly scattering tissues and imaging can be performed at 1-2 pm resolution. The hypothesis of this proposal is that OCT can detect Barrett's epithelium underlying the esophageal squamous epithelium during endoscopy. The specific aims of this proposal are to develop an OCT system along with a compact X-Y scanning probe that can perform real time imaging at 1.5 pm resolution. The OCT probe will be used to image ex vivo esophagectomy specimens from Barrett's patients to determine if it is feasible to detect Barrett's epithelium underneath squamous epithelium. In addition, an OCT balloon catheter will be developed that permits stabilization and systematic imaging of the esophagus over a large area. The OCT balloon catheter will be characterized on ex vivo resected swine esophagi and finally will be perfected for use during in vivo endoscopy in anesthetized swine. Imaged tissues will be processed for histology to compare with the OCT images. If successful, this technology could also be used to detect premalignant conditions (such as dysplasia) and early cancer. It is anticipated that a larger, longer term grant will be required for further refinements of the technology and for determining the prevalence of residual Barrett's under squamous epithelium following various types of endoscopic ablation procedures.